ZOOL 1073 Foundations of Pathophysiology - Module 1

Introduction and Text Resources

• Course Title: ZOOL 1073 Foundations of Pathophysiology.

• Primary Topic: Introduction to Pathophysiology.

• Required Reading Resources:

  • 2nd Can. Ed. Understanding Pathophysiology: p. xiii

  • 1st Can. Ed. Understanding Pathophysiology: p. x

  • 8th Ed. Pathophysiology: p. xiii-xiv

  • 7th Ed. Pathophysiology: p. xv – xvi

Definition and Importance of Pathophysiology

• Pathophysiology: The study of functional changes that occur to cells, tissues, and organs resulting from disease or injury.

• Underlying Alterations: Functional changes may arise from structural, mechanical, physiological, or biochemical alterations at the genetic or cellular levels.

• Relevance to Nursing Practice:

  • Understanding pathophysiology allows nurses to recognize the underlying mechanisms of disease manifesting as clinical signs and symptoms.

  • Nurses utilize pathophysiology knowledge in every patient care interaction to bridge the gap between patient data and clinical understanding.

Disease vs. Illness

• Disease:

  • An abnormal condition representing a homeostatic imbalance.

  • Causes variations in cellular structure or function outside of the normal range, resulting in a loss of balance required for optimal cellular function.

  • Clinical Indicators: Can be detected via diagnostic tools such as diagnostic proof, medical history, and clinical manifestations.

• Illness:

  • Refers to the individual's subjective experience of feeling "unhealthy."

  • Suggests the individual is aware of the homeostatic imbalance (i.e., one "feels" ill while they "have" a disease).

• Comparison Table Metrics:

  • Diagnostic Tools: Disease utilizes Blood chemistry, Imaging, and DNA analysis; Illness relies on Medical History.

  • Physical State: Disease involves homeostatic imbalance; Illness involves feeling unhealthy.

  • ADLs (Activities of Daily Living): In disease, an individual may adapt and continue ADLs; in illness, there is often difficulty with ADLs.

• Diagnostic Examples:

  • Blood Chemistry: Measuring blood glucose ($BG$), blood $pH$, $PO_2$, or intracellular enzymes in extracellular fluids (plasma).

  • Cardiac Biomarkers: Elevated blood levels of troponin and creatinine phosphokinase ($CPK$) indicate myocardial ischemia or infarction.

  • Imaging: X-rays, ultrasound, CT scans, and MRI scans.

  • DNA Analysis.

Core Topics in Pathophysiology

• Pathophysiology encompasses four interrelated topics:

  1. Etiology: The cause of the disease.

  2. Pathogenesis: The progression/evolution of the disease.

  3. Clinical Manifestations: The signs and symptoms.

  4. Treatment: Management of the condition (addressed in separate nursing courses).

Etiology: The Cause of Disease

• Etiology is the study of the causes of disease or injury.

• Three Broad Categories:

  1. Genetic Etiology: Cause is a genetic abnormality.

  2. Congenital Etiology: Condition present at birth, often due to in utero factors.

  3. Acquired Etiology: Damage occurs after birth (most common category).

Genetic Etiology

• Fundamental Concepts:

  • Genes: Specific regions of DNA coding for and regulating protein synthesis.

  • Gene Expression: The process of protein synthesis via transcription ($DNA \rightarrow mRNA$) and translation ($mRNA \rightarrow amino acid sequence$).

  • Genetic Disorders: Diseases altering DNA nucleotide sequences ($A, T, C, G$) caused by mutations in one or multiple genes or combinations of genes and environmental factors.

• Causes of Genetic Disorders:

  1. Inherited traits: Familial predispositions running in families.

  2. Random: Spontaneous mutations.

  3. Environmental Exposure: Exposure to substances that cause mutations.

• Chromosomal Defect/Mutation:

  • Additions, deletions, or translocations of sections of chromosomes (e.g., $5p$ minus syndrome/Cri du Chat involving deletion of the short arm of chromosome 5).

  • Aneuploidy: Additions or deletions of entire chromosomes (e.g., Trisomy $21$, Turner syndrome $45X$ or $45XO$).

  • Risk Factor: Advanced maternal age increases the risk of chromosomal abnormalities.

• Single Gene Defect/Genetic Mutation:

  • Addition, deletion, or switching of a single nitrogenous base ($A, T, C, G$) leading to defective protein synthesis.

  • Examples: Cystic fibrosis, hemophilia, sickle cell disease, and phenylketonuria ($PKU$).

  • Environmental influences: Lung or urinary bladder cancer resulting from cigarette smoke.

• Clinical Manifestations:

  • Developmental effects: Down syndrome (Trisomy $21$) manifests with learning disorders, cardiac abnormalities, and early-onset dementia.

  • Disease Susceptibility: UV skin damage susceptibility based on complexion; early-onset heart disease in families with hypercholesterolemia.

Congenital Etiology

• Definition: Structural or functional anomalies occurring during embryonic/fetal development in utero or during labor and delivery.

• Prevalence: Approximately $6\%$ of babies worldwide are born with congenital anomalies ($94\%$ in low or middle-income families).

• Timing of Exposure:

  • Embryonic Development: Week $3$ to end of week $8$; most dangerous period for teratogen exposure causing severe malformations.

  • Fetal Development: Week $9$ to birth; developmental issues are usually less severe than embryonic exposure.

• Causes:

  • Injury during pregnancy, labor, or delivery.

  • Exposure to Teratogens: Substances or conditions impairing development (e.g., infections, chemicals, radiation).

  • Micronutrient Deficiencies: Lack of folic acid (neural tube defects like spina bifida); lack of iodine (hypothyroidism and impaired neurological development).

  • Consanguinity: Parents closely related by blood.

  • Advanced Maternal Age: Increased risk of chromosomal issues.

• The TORCH Acronym (Common Teratogens):

  • T: Toxoplasmosis.

  • O: Other (Coxsackie virus, Hepatitis, HIV, Parvovirus, Syphilis, Varicella-Zoster, Zika, Lyme disease; Chemicals like nicotine/maternal smoking causing low birth weight ($LBW$) via vasoconstriction; Alcohol causing Fetal Alcohol Spectrum Disorder ($FASD$); Maternal diabetes; Radiation; Thalidomide).

  • R: Rubella.

  • C: Cytomegalovirus.

  • H: Herpes simplex 2.

• Clinical Manifestations: Structural anomalies (heart defects, club foot, deafness, cleft palate, cerebral palsy) or functional issues (blindness, sensory/motor/cognitive deficits).

Acquired Etiology

• Definition: Damage occurs after birth to an individual with normal genetic and intrauterine development.

• General Causes:

  • Infectious agents (microbial/biological).

  • Physical and chemical agents.

  • Malnutrition (nutritional, fluid, electrolyte, and $pH$ imbalances).

  • Abnormal immune responses.

  • Psychological agents.

• Specific Terminology:

  • Idiopathic: The cause of the disease is unknown.

  • Iatrogenic: The cause is related to a medical intervention (e.g., surgical procedures, drug side effects).

  • Nosocomial (Health care-associated): Acquired in a hospital environment (e.g., $Clostridium\,difficile$, healthcare workers contracting Covid-19).

• Physiological pH and Imbalance:

  • Normal range: $7.35 - 7.45$ (Average $7.4$).

  • Acidosis: Blood $pH$ < $7.35$.

  • Alkalosis: Blood $pH$ > $7.45$.

  • Respiratory Acidosis: Caused by hypoventilation (increased $CO_2$).

  • Respiratory Alkalosis: Caused by hyperventilation (decreased $CO_2$).

  • Metabolic Acidosis: Caused by acidic drug overuse, diarrhea, or Diabetic Ketoacidosis ($DKA$).

  • Metabolic Alkalosis: Caused by basic drug overuse or vomiting.

  • Critical Thresholds: pH < 7.2 - 7.3 leads to Loss of Consciousness ($LOC$) or coma; pH > 7.5 - 8.0 leads to convulsions and then $LOC$.

Pathogenesis, Lesions, and Tissue Types

• Pathogenesis: The pattern of structural and functional changes leading to disease development. It explains how a disease evolves over time from initial contact with an etiological agent to the appearance of clinical manifestations.

• Principal Elements of Pathogenesis: Etiological agent $\rightarrow$ Initial injury $\rightarrow$ Defective cellular/tissue function $\rightarrow$ Defective organ function $\rightarrow$ Signs and symptoms $\rightarrow$ Systemic effects.

• Lesions: The actual sites of tissue damage (the "wound").

  • Local/Focal: Limited to a specific, defined body location.

  • Diffuse (Multifocal): Damage distributed throughout a larger area of a specific organ or system.

  • Systemic: Widespread damage affecting more than one organ or organ system (e.g., metastatic cancer).

• Organ Components:

  • Parenchyma: The functional cells of the organ (e.g., skeletal muscle cells, neurons in the CNS).

  • Stroma: The supportive framework (connective tissue, fibroblasts, extracellular matrix, microvasculature, lymphatics, and nerve endings).

• Morphological Change: Alterations in cell shape or size. Cells adapt to survive chronic injury, but change may impair function.

  • Note: Morphological changes can be non-pathologic (e.g., uterine changes during pregnancy).

Clinical Manifestations and Syndromes

• Signs: Objective, detectable, and testable information obtained through physical exams, labs (vital signs, $BG$, imaging, biopsy).

• Symptoms: Subjective experiences reported by the patient (pain level, malaise, anxiety, headache).

• Syndrome: A disease/condition with a defined group of lesions and clinical manifestations linked to a common etiology.

  • Examples:

    • Down Syndrome (Genetic: Trisomy $21$).

    • AIDS (Acquired: HIV infection).

    • Fetal Alcohol Syndrome (Congenital: Alcohol exposure).

    • Reye Syndrome: Often follows ASA (Aspirin) use for viral infections in children; causes liver damage and encephalopathy.

    • Metabolic Syndrome: Comorbidities of high $BG$, abdominal obesity, and high cholesterol.

Risk Factors and Prognostic Terms

• Predisposing Risk Factors: Increase the possibility of developing a disease (e.g., family history of heart disease).

• Precipitating Risk Factors: Factors that actually trigger the disease/injury (e.g., smoking leading to atherosclerosis).

• Modifiable Factors: Lifestyle and environment.

• Non-modifiable Factors: Age, genetics, biological sex.

• Complications: New disease or condition occurring in addition to original damage.

• Sequelae: Long-term, unwanted outcomes or chronic health issues resulting from a disease (e.g., rheumatic fever causing heart damage; "long Covid").

• Comorbidity: Two or more concurrent diseases present in a patient (e.g., obesity and arthritis).

Disease Onset and Course

• Onset Classifications:

  • Acute Onset: Sudden, severe, short duration (e.g., food poisoning, myocardial infarction, broken leg).

  • Chronic Onset: Continuous, long duration (e.g., Hypertension, Cystic Fibrosis).

  • Insidious Onset: Subset of chronic; often unnoticed for long periods (e.g., Alzheimer’s).

  • Latent/Dormant: Asymptomatic period of quiescence (e.g., HIV, shingles).

  • Subclinical/Subacute: Intermediate between acute and chronic; symptoms and signs may be subtle (e.g., subacute endocarditis).

• Clinical Disease Course: Progression over time.

  • Remissions: Periods where manifestations disappear or decrease.

  • Exacerbations: "Flare-ups" where manifestations become more severe (e.g., Multiple Sclerosis).

Infectious Disease Course

1. Incubation Period: Time between exposure and first symptoms; individual is asymptomatic but may be contagious.

2. Prodromal Stage: Initial non-specific symptoms (tiredness, discomfort); most contagious stage.

3. Invasion Period: Rapid multiplication and spread; specific clinical manifestations present (pain, malaise, rashes; fever indicates systemic infection).

4. Convalescence: Recovery time; individual should no longer be contagious.

Epidemiology Terminology

• Prevalence: Number of existing cases in a population at a specific time (Common vs. Rare).

• Incidence: Number of new cases in a population during a specific time.

• Endemic: Constant rates of infection within a specific population (e.g., Malaria in parts of Africa, TB in Northern Canada).

• Epidemic: New infections far exceed expected levels (e.g., Ebola in West Africa).

• Pandemic: An epidemic spread over a large area (continental or global).

• Notifiable (Reportable) Disease: Required by law to be reported to public health authorities (e.g., PHAC definitions).

• Mortality Rate: Death rate due to a specific cause in a population.

• Morbidity Rate: Incidence/rate of a specific disease, impacting long-term health and healthcare costs.

Questions & Discussion

• Matching Activity - Acquired Etiology:

  • "I went to the hospital to have my baby and now I have a bad gut infection.": Nosocomial.

  • Nurse did not properly wash hands prior to changing a surgical dressing: Iatrogenic.

  • "I'm sorry but we don't know the cause of the seizure.": Idiopathic.

• Syndrome Etiology Matching:

  • Down Syndrome: Genetic Etiology.

  • Acquired Immunodeficiency Syndrome (AIDS): Acquired Etiology.

  • Fetal Alcohol Syndrome: Congenital Etiology.

  • Reye Syndrome: Acquired Etiology.

  • Metabolic Syndrome: Multifactorial.